Feliz Navidad

It's Christmas Eve! I want to wish everyone a Merry Christmas. This is such a special time of year. Tonight I'm singing Ave Maria in the Children's Mass. I'm really excited! Last year, I got to be Mary.

Our Christmas tree is up. And all of our presents are wrapped. My Dad has been making lots of yummy food. I can't wait to eat our Christmas Eve dinner tonight!

Merry Chirstmas! I hope you get everything on your list! :) C

Good News for Armchair Neuropathologists

Ever wanted to crack the mysteries of the brain? Dreamed of discovering the cause of mental illness?

Well, now, you can - or, at any rate, you can try - and you can do it from the comfort of your own home, thanks to the new Stanley Neuropathology Consortium Integrative Database.

Just register (it's free and instant) and you get access to a pool of data derived from the Stanley Neuropathology Consortium brain collection. The collection comprises 60 frozen brains - 15 each from people with schizophrenia, bipolar disorder, and clinical depression, and 15 "normals".

In a Neuropsychopharmacology paper announcing the project, administrators Sanghyeon Kim and Maree Webster point out that

Data sharing has become more important than ever in the biomedical sciences with the advance of high-throughput technology and web-based databases are one of the most efficient available resources to share datasets.

The Institute's 60 brains have long been the leading source of human brain tissue for researchers in biological psychiatry. Whenever you read about a new discovery relating to schizophrenia or bipolar disorder, chances are the Stanley brains were involved. The Institute provide slices of the brains free of charge to scientists who request them, and they've sent out over 200,000 to date.

Until now, if you wanted to find out what these scientists discovered about the brains, you'd have to look up the results in the many hundreds of scientific papers where the various results were published. If you knew where to look, and if you had a lot of time on your hands. The database collates all of the findings. That's a good idea. To ensure that they get all of the results, the Institute have another good idea:

Coded specimens are sent to researchers with the code varying from researcher to researcher to ensure that all studies are blinded. The code is released to the researcher only when the data have been collected and submitted to the Institute.

The data we're provided about the brains is quite exciting, if you like molecules, comprising 1749 markers from 12 different parts of the brain. Markers include levels of proteins, RNA, and the number and shape of various types of cells.

It's easy to use. While waiting for my coffee to brew, I compared the amount of the protein GFAP76 in the frontal cortex between the four groups. There was no significant difference. I guess GFAP76 doesn't cause mental illness - darn. So much for my Nobel Prize winning theory. But I did find that levels of GFAP76 were very strongly correlated with levels of another protein, "phosphirylated" (I think they mean "phosphorylated") PRKCA. You read it here first.

In the paper, Kim and Webster used the Database to find many differences between normal brains and diseased brains, including increased levels of dopamine in schizophrenia, and increased levels of glutamate in depression and bipolar. And decreased GAD67 proteins in the frontal cortex in bipolar and schizophrenia. And decreased reelin mRNA in the frontal cortex and cerebellum in bipolar and schizophrenia. And...

This leaves open the vital questions of what these differences mean, as I have complained before. And the problem with giving everyone in the world the results of 1749 different tests, and letting us cross-correlate them with each other and look for differences between 4 patient groups, is that you're making possible an awful lot of comparisons. With only 15 brains per group, none of the results can be considered anything more than provisional, anyway - what we really need are lots more brains.

But this database is still a welcome move. This kind of data pooling is the only sensible approach to doing modern science, and it's something people are advocating in other fields of neuroscience as well. It just makes sense to share results rather than leaving everyone to do there own thing in near-isolation from each other, now that we have the technology to do so. In fact, I'd say it's a... no-brainer.

Kim, S., & Webster, M. (2009). The Stanley Neuropathology Consortium Integrative Database: a Novel, Web-Based Tool for Exploring Neuropathological Markers in Psychiatric Disorders and the Biological Processes Associated with Abnormalities of Those Markers Neuropsychopharmacology, 35 (2), 473-482 DOI: 10.1038/npp.2009.151

Good News for Armchair Neuropathologists

Ever wanted to crack the mysteries of the brain? Dreamed of discovering the cause of mental illness?

Well, now, you can - or, at any rate, you can try - and you can do it from the comfort of your own home, thanks to the new Stanley Neuropathology Consortium Integrative Database.

Just register (it's free and instant) and you get access to a pool of data derived from the Stanley Neuropathology Consortium brain collection. The collection comprises 60 frozen brains - 15 each from people with schizophrenia, bipolar disorder, and clinical depression, and 15 "normals".

In a Neuropsychopharmacology paper announcing the project, administrators Sanghyeon Kim and Maree Webster point out that

Data sharing has become more important than ever in the biomedical sciences with the advance of high-throughput technology and web-based databases are one of the most efficient available resources to share datasets.

The Institute's 60 brains have long been the leading source of human brain tissue for researchers in biological psychiatry. Whenever you read about a new discovery relating to schizophrenia or bipolar disorder, chances are the Stanley brains were involved. The Institute provide slices of the brains free of charge to scientists who request them, and they've sent out over 200,000 to date.

Until now, if you wanted to find out what these scientists discovered about the brains, you'd have to look up the results in the many hundreds of scientific papers where the various results were published. If you knew where to look, and if you had a lot of time on your hands. The database collates all of the findings. That's a good idea. To ensure that they get all of the results, the Institute have another good idea:

Coded specimens are sent to researchers with the code varying from researcher to researcher to ensure that all studies are blinded. The code is released to the researcher only when the data have been collected and submitted to the Institute.

The data we're provided about the brains is quite exciting, if you like molecules, comprising 1749 markers from 12 different parts of the brain. Markers include levels of proteins, RNA, and the number and shape of various types of cells.

It's easy to use. While waiting for my coffee to brew, I compared the amount of the protein GFAP76 in the frontal cortex between the four groups. There was no significant difference. I guess GFAP76 doesn't cause mental illness - darn. So much for my Nobel Prize winning theory. But I did find that levels of GFAP76 were very strongly correlated with levels of another protein, "phosphirylated" (I think they mean "phosphorylated") PRKCA. You read it here first.

In the paper, Kim and Webster used the Database to find many differences between normal brains and diseased brains, including increased levels of dopamine in schizophrenia, and increased levels of glutamate in depression and bipolar. And decreased GAD67 proteins in the frontal cortex in bipolar and schizophrenia. And decreased reelin mRNA in the frontal cortex and cerebellum in bipolar and schizophrenia. And...

This leaves open the vital questions of what these differences mean, as I have complained before. And the problem with giving everyone in the world the results of 1749 different tests, and letting us cross-correlate them with each other and look for differences between 4 patient groups, is that you're making possible an awful lot of comparisons. With only 15 brains per group, none of the results can be considered anything more than provisional, anyway - what we really need are lots more brains.

But this database is still a welcome move. This kind of data pooling is the only sensible approach to doing modern science, and it's something people are advocating in other fields of neuroscience as well. It just makes sense to share results rather than leaving everyone to do there own thing in near-isolation from each other, now that we have the technology to do so. In fact, I'd say it's a... no-brainer.

Kim, S., & Webster, M. (2009). The Stanley Neuropathology Consortium Integrative Database: a Novel, Web-Based Tool for Exploring Neuropathological Markers in Psychiatric Disorders and the Biological Processes Associated with Abnormalities of Those Markers Neuropsychopharmacology, 35 (2), 473-482 DOI: 10.1038/npp.2009.151

Yummy Comida!

Dad made some yummy green chili stew and tortillas tonight for dinner. It was so good. And it warmed us all up. It's so cold outside! I ate 2 bowls of stew and 3 tortillas. 1 of them with butter. Fresh off the placa. It was the best one!

I also made a chocolate cake. Mi abuelita helped me with the frosting. We make our own. It is so yummy! I baked 2 cakes and we stacked them. Mi abuelita make some chocolate and raspberry filling to put between them. And then we frosted the cake with chocolate icing. After dinner, we each had a big piece with a glass of milk. My belly is all full now!

Tonight, I need to work on dad's Christmas present. I only have a few days left to finish it! But it's almost done. I'm not too worried about it yet. I think I can finish it tonight. Maybe in the morning. I'm not sure. But that is what I'm working on tonight. :) C

The Guineapigs

Before waterboarding, there was wall standing.

The Guineapigs is a book by John McGuffin. It was published in 1974, at the height of "The Troubles" in Northern Ireland, and banned in Britain almost immediately.

The "guineapigs" in question were 14 men from Northern Ireland detained by British security forces during the 1971 campaign of internment of suspected Irish Republican Army militants and sympathizers. The book details the treatment they experienced in the week after their detention, specifically "sensory deprivation".

The men were forced to stand up against a wall, with a black hood over their head, in a room into which a loud noise - described as something like a jet engine or gushing water - was played. If they fell or otherwise moved from this stance, they were forced back up. This went on for up to 48 hours, during which time they were given neither food nor sleep.

After this the treatment became a bit less harsh, and they were interrogated at various intervals. After about a week, they were released into a "normal" prison, and the story came out. A government inquiry, the Compton Report, followed, confirming that the "Questioning in Depth" had occurred but denying that it constituted "brutality".

The Guineapigs contains first person accounts from several of the men, describing the disorientation, hallucinations and terror they experienced during the procedure, and also details the psychological after-effects they reportedly suffered, including several cases of mental illness and at least psychiatric hospitalization.

McGuffin's most controversial claim was that the whole thing was a psychological experiment. It could not, he said, have been meant to gather useful information per se, because the 14 "subjects" were not especially high-value suspects; they seemed to have been chosen at random from the hundreds interned. Instead, he said, it was a research project, a trial of the technique of sensory deprivation as torture.

During the 1960s and 1970s there was lots of academic research on sensory deprivation, in which volunteers often reported hallucinations, paranoia, mood changes and other "psychotic" symptoms after being deprived of sight, sound and touch stimuli for a few hours. According to McGuffin, the British government decided to "field test" to procedure to see whether the same thing happened in "real life" with test subjects who weren't willing volunteers.

I'm not sure whether to believe this explanation of what happened; McGuffin was hardly an unbiased observer - he was himself interned in 1971, although he wasn't amongst the guineapigs - and he was a lifelong opponent of British rule in Northern Ireland. We'll probably never know for sure. But maybe it's as convincing as any other explanation.

Links: Lots of the book is online here. Mind Hacks on a recent sensory deprivation study, and a documentary about s.d. interrogation during WW2. I found a paper by T Shallice (1972) on The Ulster depth interrogation techniques and their relation to sensory deprivation research, but I haven't been able to access it yet. John McGuffin obits.

The Guineapigs

Before waterboarding, there was wall standing.

The Guineapigs is a book by John McGuffin. It was published in 1974, at the height of "The Troubles" in Northern Ireland, and banned in Britain almost immediately.

The "guineapigs" in question were 14 men from Northern Ireland detained by British security forces during the 1971 campaign of internment of suspected Irish Republican Army militants and sympathizers. The book details the treatment they experienced in the week after their detention, specifically "sensory deprivation".

The men were forced to stand up against a wall, with a black hood over their head, in a room into which a loud noise - described as something like a jet engine or gushing water - was played. If they fell or otherwise moved from this stance, they were forced back up. This went on for up to 48 hours, during which time they were given neither food nor sleep.

After this the treatment became a bit less harsh, and they were interrogated at various intervals. After about a week, they were released into a "normal" prison, and the story came out. A government inquiry, the Compton Report, followed, confirming that the "Questioning in Depth" had occurred but denying that it constituted "brutality".

The Guineapigs contains first person accounts from several of the men, describing the disorientation, hallucinations and terror they experienced during the procedure, and also details the psychological after-effects they reportedly suffered, including several cases of mental illness and at least psychiatric hospitalization.

McGuffin's most controversial claim was that the whole thing was a psychological experiment. It could not, he said, have been meant to gather useful information per se, because the 14 "subjects" were not especially high-value suspects; they seemed to have been chosen at random from the hundreds interned. Instead, he said, it was a research project, a trial of the technique of sensory deprivation as torture.

During the 1960s and 1970s there was lots of academic research on sensory deprivation, in which volunteers often reported hallucinations, paranoia, mood changes and other "psychotic" symptoms after being deprived of sight, sound and touch stimuli for a few hours. According to McGuffin, the British government decided to "field test" to procedure to see whether the same thing happened in "real life" with test subjects who weren't willing volunteers.

I'm not sure whether to believe this explanation of what happened; McGuffin was hardly an unbiased observer - he was himself interned in 1971, although he wasn't amongst the guineapigs - and he was a lifelong opponent of British rule in Northern Ireland. We'll probably never know for sure. But maybe it's as convincing as any other explanation.

Links: Lots of the book is online here. Mind Hacks on a recent sensory deprivation study, and a documentary about s.d. interrogation during WW2. I found a paper by T Shallice (1972) on The Ulster depth interrogation techniques and their relation to sensory deprivation research, but I haven't been able to access it yet. John McGuffin obits.

Neuroskeptic Gets "Cited"

...kind of. Last week, I blogged about a Nature paper, Eisenegger et al, reporting that giving women testosterone makes them behave more generously in a money-sharing procedure called the Ultimatum Game.

But just a few days later, PLoS ONE published a paper, Zak et al, finding exactly the opposite result - testosterone decreased generosity in the Ultimatum Game - although that was in men, rather than women. The lead author of the PLoS paper, Paul J. Zak, then "cited" my blog post in an online comment attached to his article, as part of a discussion of the differences between his paper and Eisenegger et al's. This is not a proper citation of course, but it's a start. At least I like to think so.

PLoS have a brilliant policy of having a blog-style comment thread attached to every paper. This is a far better system than the traditional academic policy of allowing comments only in the form of formal "Letters to the Editor" of the journal. This made sense in the days before the internet, but it's long outlived its usefulness.

A Letter has to be approved by the editor of the journal to get published at all. For reasons of space, if nothing else, the number which get printed is small. Even if your Letter does see the light of day, it will be, at minimum, a couple of months after the original paper was published, by which time most readers of the original will have forgotten what the fuss was about. If the original authors reply to your Letter, and you want to reply to their reply, it'll be another couple of months before you can, assuming you still care about it by this point. And so on.

An online comment thread, on the other hand, is "peer review" in its purest form. The key difference is speed - replies take place in real time or close to it, which makes a genuine conversation possible. The fact that anyone on the internet can comment might not seem to be a good thing; the internet makes you stupid, after all. But the standard of comments on PLoS papers is generally very high; I don't know if this is because of a moderation policy, or just because PLoS readers are sensible folk.

A few other journals have adopted a similar commenting system, notably Nature (although apparently not other Nature group journals like Nature Neuroscience), but this is something I'd like to see all journals adopt. Ultimately, I'd like to see the boundaries between the "official" academic literature and "informal" online discussion such as blogs blurred further; PLoS seem to be leading the way in this regard too with their recently announced integration with ResearchBlogging.org although Nature also have a blog section. Exciting times.